BAD is a condition characterised by mood swings (mania and depression) that affects 1-2% of the population. Twin and adoption studies have shown that this disorder has a strong genetic component. However, it has a complex genetic basis and increased susceptibilty is likely due to the interplay of a number of distinct genes. The identification of a number of positive linkage results at differing chromosomal positions which supports this model of a complex genetic aetiology. Possible susceptibility loci have been reported on chromosomes 4p, 18p, 18q and 21q (Berrettini et al., 1994; Straub et al., 1994; Gurlinig et al., 1995: Stine et al., 1995; Blackwood et al., 1996: De bruyn et al., 1996: Coon et al. 1996; Freimer et al., 1996). However, no predisposing genes have ,et been identified. The present inventors have conducted a 15-cM genome screen of 214 microsatellite markers on 35 individuals from a large Australian pedigree with a history of BAD. Data were analysed by parametric two-point linkage methods using several diagnostic models. Lod scores &gt;1.00 were obtained for 21 markers, with four of these &gt;2.00 for at least one model. The remaining 52 individuals in the family were then genotyped with these four markers and lod scores remained positive for three markers. A more intensive screen was undertaken in these regions with the most positive results being obtained for chromosome 4q35. Using a dominant model of inheritance with 90% maximum age-specific penetrance and including bipolar I, II, schizoaffective/mania and unipolar individuals as affected, a maximum two-point lod score of 2.20 (.theta.=0.15) at D4S1652 was obtained and a maximum three-point lod score of 3.19 obtained between D4S408 and D4S2924 was obtained. Non-parametric analyses further supported the presence of a predisposing locus on chromosome 4q35. A maximised score of 2.62 (p=0.01) was obtained between D4S1652 and D4S171 using the GENEHUNTER program, and a maximum score of 3.57(p=0.0002) was obtained at D4S2924 using the affected pedigree member (APM) method. Analysis of a further twenty-three pedigrees suggested the presence of this susceptibility locus in at least three additional families, indicating a predisposing susceptibiliy locus and not a pedigree-specific mutation. The results suggest the presence of a BAD susceptibility locus on chromosome 4q35.